Immunogenic ovarian cancer genes

Abstract

The present invention is based on the discovery of autoantibodies in cancer patients specific for a number of antigens that are normally intracellular, including homeobox protein HOXA7, homeobox protein HOXB7, ADP-ribosylation factor 1 (Arf-1), ATP-dependent iron transporter ABC-7, and a novel protein encoded by a EcoRI/XhoI fragment of bacteriophage λ clone 44B.1 deposited under ATCC accession No. ______. The presence of these autoantibodies can be correlated with neoplastic processes in patients, and therefore detection of autoantibodies (or detection of expression of the antigens by other means) can be used as a component of a cancer screening program. The present invention provides such screening assays. In addition, the studies leading to the identification of the predictive autoantigens have also succeeded in identifying a hitherto unknown antigen that is disclosed herein.

1 . A substantially pure nucleic acid characterized by at least one of (a) homology with a EcoRI/XhoI fragment isolated from bacteriophage λ clone 44B.1 deposited under ATCC accession No. ______ PTA-3170, wherein homologous sequences have a sequence alignment score of greater than 200 as calculated by BLASTN 2.1.2: (b) hybridization to a EcoRI/XhoI fragment isolated from bacteriophage λ clone 44B.1 deposited under ATCC accession No. PTA-3170 under stringent hybridization conditions, wherein stringent hybridization conditions comprise 0.5 MNaHPO 4 /1 mM EDTA/7%(w/v) SDS at 55° C.; and (c) said nucleic acid encoding the amino acid sequence encoded by the EcoRI/XhoI fragment isolated from bacteriophage λ clone 44B.1 deposited under ATCC Accession No. PTA-3170.  
     
     
         2 - 8 . (canceled)  
     
     
         9 . A pair of nucleic acid primers comprising at least 10 contiguous nucleotides selected from or complementary to a portion of a EcoRI/XhoI fragment isolated from bacteriophage λ clone 44B.1 deposited under ATCC accession No. ______ PTA-3170, wherein nucleic acid amplification using the pair of nucleic acid primers will produce an amplified nucleic acid comprising at least 18 contiguous nucleotides of the nucleic acid of  claim 1 .  
     
     
         10 . (canceled)  
     
     
         11 . A recombinant cell containing a recombinant nucleic acid comprising the nucleic acid of  claim 1 .  
     
     
         12 . A substantially pure polypeptide comprising an amino acid sequence encoded by a EcoRI/XhoI fragment isolated from bacteriophage λ clone 44B.1 deposited under ATCC accession No. ______ PTA-3170, wherein said polypeptide comprises at least one epitope.  
     
     
         13 - 14 . (canceled)  
     
     
         15 . An antibody which specifically binds to the polypeptide of  claim 12 .  
     
     
         16 . (canceled)  
     
     
         17 . A method for selecting variant nucleic acid sequences comprising (a) screening mammalian DNA or RNA with a nucleic acid probe comprising the nucleic acid of  claim 1 , (b) sequencing the DNA or RNA obtained in said screening, and (c) selecting DNA or RNA having sequences that differ from the nucleic acid sequence in a EcoRI/XhoI fragment of bacteriophage λ clone 44B.1 deposited under ATCC accession No. ______ PTA-3170, by at least one nucleotide.  
     
     
         18 . (canceled)  
     
     
         19 . A nucleic acid encoding HOXB7 having an amino acid sequence corresponding to the amino acid sequence encoded by the sequence shown as SEQ ID NO: 1.  
     
     
         20 . A protein encoded by the nucleic acid of  claim 19 .  
     
     
         21 - 29 . (canceled)  
     
     
         30 . A method of screening for cancer in an individual comprising determining whether cells in the individual are expressing at least one gene product selected from the group consisting of homeobox protein HOXA7, homeobox protein HOXB7, ADP-ribosylation factor 1 (Arf-1), ATP-dependent iron transporter ABC-7, and the protein encoded by a EcoRI/XhoI fragment of bacteriophage λ clone 44B. 1 deposited under ATCC accession No. ______ PTA-3170, expression of at least one of these gene products being correlated with an increased likelihood of cancer in the individual.  
     
     
         31 . The method according to  claim 30 , wherein said method comprises 
 determining whether cells in the individual are expressing two or more of said gene products.    
     
     
         32 - 39 . (canceled)  
     
     
         40 . A kit for screening human samples according to the method of  claim 30 , comprising in one or more containers: 
 a nucleotide probe which hybridizes to mRNA encoding said product; and    reagent means for detecting the nucleotide probe.    
     
     
         40 . (canceled)  
     
     
         41 . A method of screening for cancer in an individual comprising obtaining a sample of bodily fluid from the individual and determining whether or not the sample contains antibodies specific for one or more of the proteins selected from the group consisting of homeobox protein HOXA7, homeobox protein HOXB7, ADP-ribosylation factor 1 (Arf-1), ATP-dependent iron transporter ABC-7, and the protein encoded by a EcoRI/XhoI fragment of bacteriophage λ clone 44B.1 deposited under ATCC accession No. ______ PTA-3170, the presence of antibodies to any one of these proteins being correlated with an increased likelihood of cancer in the individual.  
     
     
         42 . A method of screening for cancer in an individual comprising obtaining a sample of bodily fluid from the individual and determining whether or not the sample contains one or more proteins selected from the group consisting of homeobox protein HOXA7, homeobox protein HOXB7, ADP-ribosylation factor 1 (Arf-1), ATP-dependent iron transporter ABC-7, and the protein encoded by a EcoRI/XhoI fragment of bacteriophage λ clone 44B.1 deposited under ATCC accession No. ______ PTA-3170, the presence of any one of these proteins in the bodily fluid being correlated with an increased likelihood of cancer in the individual.  
     
     
         43 . A method of cancer therapy comprising immunizing an individual with an immunogenic composition to elicit an immune response to one or more of the proteins selected from the group consisting of homeobox protein HOXA7, homeobox protein HOXB7, ADP-ribosylation factor 1 (Arf-1), ATP-dependent iron transporter ABC-7, and the protein encoded by a EcoRI/XhoI fragment of bacteriophage λ clone 44B.1 deposited under ATCC accession No. ______ PTA-3170.  
     
     
         44 - 45 . (canceled)